1. Field of the Invention
This invention relates to derivatives of cyclic ketals of N-alkylimidazoles and the antimicrobial acid addition salts thereof, which are useful as antimicrobial agents. The invention also relates to compositions containing an effective amount of at least one of the compounds in combination with a suitable excipient, the composition being useful for combatting fungi, bacteria and protozoa. The invention also relates to novel intermediates and to a process for making the compounds of the invention.
2. Related Disclosures
Compounds of the following formula are known ##STR2## wherein: R.sup.1 is, i.a., phenyl optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, alkoxy, nitro, and cyano;
R.sup.2 is, i.a., phenyl or benzyl wherein the phenyl ring of R.sup.2 is optionally substituted by one or more substituents selected from the group consisting of halo, alkyl, alkoxy, and phenyl; PA1 Z is oxygen or sulfur; and when Z is oxygen R.sup.2 may be hydrogen. See U.S. Pat. Nos. 3,936,470, 4,101,664, 4,101,665, 4,101,666 and 4,144,346, and Great Britain Pat. No. 1,528,639. PA1 R.sup.1 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl; PA1 R.sup.2 is phenyl or benzyl wherein the phenyl ring of R.sup.2 is optionally substituted by one or more substituents selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl; or by a phenyl optionally substituted by halo, lower alkyl, lower alkoxy or trifluoromethyl; and PA1 the antimicrobial acid addition salts thereof. PA1 R.sup.1 is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl; PA1 R.sup.2 is phenyl or benzyl wherein the phenyl ring of R.sup.2 is optionally substituted by one or more substituents selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl; or a phenyl optionally substituted by halo, lower alkyl, lower alkoxy or trifluoromethyl; and PA1 the antimicrobial acid addition salts thereof. PA1 Microsporum audouini, PA1 Microsporum gypseum, PA1 Microsporum gypseum-canis, PA1 Epidermophyton floccosum, PA1 Trichophyton mentagrophytes, PA1 Trichophyton rubrum PA1 Trichophyton tonsurans PA1 Candida albicans, and PA1 Cryptococcus neoformans. PA1 Aspergillus flavus, PA1 Cladosporium herbarum, PA1 Fusarium graminearum, PA1 Penicillium notatum, PA1 Aspergillus niger, PA1 Penicillium oxalicum, PA1 Penicillium spinulosum, and PA1 Pithomyces chartarum. PA1 Staphylococcus aureus, PA1 Streptococcus faecalis, PA1 Corynebacterium acnes, PA1 Erysipelothrix insidiosa, PA1 Escherischia coli, PA1 Proteus vulgaris, PA1 Salmonella choleraesuis, PA1 Pasterurella multocida, and PA1 Pseudomonas aeruginosa. PA1 1-chloro-4-phenyl-2-butanone, PA1 1-chloro-4-(4-bromophenyl)-2-butanone, PA1 1-chloro-4-(4-fluorophenyl)-2-butanone, PA1 1-chloro-4-(2,4-dichlorophenyl)-2-butanone, PA1 1-chloro-4-(2,4,6-trichlorophenyl)-2-butanone, PA1 1-chloro-4-(4-methylphenyl)-2-butanone, PA1 1-chloro-4-(4-t-butylphenyl)-2-butanone, PA1 1-chloro-4-(4-methoxyphenyl)-2-butanone, and PA1 1-chloro-4-(4-n-butoxyphenyl)-2-butanone. PA1 1-[4-phenylbutan-2-on-1-yl]imidazole, PA1 1-[4-(4-bromophenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(4-fluorophenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(2,4-dichlorophenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(2,4,6-trichlorophenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(4-methylphenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(4-t-butylphenyl)butan-2-on-1-yl]imidazole, PA1 1-[4-(4-methoxyphenyl)butan-2-on-1-yl]imidazole, and PA1 1-[4-(4-n-butoxyphenyl)butan-2-on-1-yl]imidazole. PA1 1-[[2-(2-phenylethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imidazole, PA1 1-[[2-(2-(4-bromophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imi dazole, PA1 1-[[2-(2-(4-fluorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(2,4-dichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methy l]imidazole, PA1 1-[[2-(2-(2,4,6-trichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]me thyl]imidazole, PA1 1-[[2-(2-(4-methylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(4-t-butylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, PA1 1-[[2-(2-(4-methoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, and PA1 1-[[2-(2-(4-n-butoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl] imidazole. PA1 2-bromomethyl-2-(2-phenylethyl)-4-benzoyloxymethyl-1,3-dioxolane, PA1 2-bromomethyl-2-[2-(4-bromophenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolane, PA1 2-bromomethyl-2-[2-(4-fluorophenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolane, PA1 2-bromomethyl-2-[2-(2,4-dichlorophenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxol ane, PA1 2-bromomethyl-2-[2-(2,4,6-trichlorophenyl)ethyl]-4-benzoyloxymethyl-1,3-dio xolane, PA1 2-bromomethyl-2-[2-(4-methylphenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolane, PA1 2-bromomethyl-2-[2-(4-t-butylphenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolane PA1 2-bromomethyl-2-[2-(4-methoxyphenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolane , and PA1 2-bromomethyl-2-[2-(4-n-butoxyphenyl)ethyl]-4-benzoyloxymethyl-1,3-dioxolan e. PA1 1-[[2-(2-phenylethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imidazole, PA1 1-[[2-(2-(4-bromophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imi dazole, PA1 1-[[2-(2-(4-fluorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(2,4-dichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methy l]imidazole, PA1 1-[[2-(2-(2,4,6-trichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]me thyl]imidazole, PA1 1-[[2-(2-(4-methylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(4-t-butylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, PA1 1-[[2-(2-(4-methoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, and PA1 1-[[2-(2-(4-n-butoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl] imidazole. PA1 1-[[2-(2-phenylethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imidazole, PA1 1-[[2-(2-(4-bromophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]imi dazole, PA1 1-[[2-(2-(4-fluorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(2,4-dichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methy l]imidazole, PA1 1-[[2-(2-(2,4,6-trichlorophenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]me thyl]imidazole, PA1 1-[[2-(2-(4-methylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]im idazole, PA1 1-[[2-(2-(4-t-butylphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, PA1 1-[[2-(2-(4-methoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl]i midazole, and PA1 1-[[2-(2-(4-n-butoxyphenyl)ethyl)-4-hydroxymethyl-1,3-dioxolan-2-yl]methyl] imidazole.